tbuckley/cabot-search huggingface dataset:
The SWI/SNF chromatin remodeling complexes BAF and PBAF differentially regulate epigenetic transitions in exhausted CD8+ T cells
Authors: Amy E. Baxter, Hua Huang, Josephine R. Giles, Zeyu Chen, Jennifer E. Wu, Sydney Drury, Katherine Dalton, Simone L. Park, Leonel Torres, Brandon W. Simone, Max Klapholz, Shin Foong Ngiow, Elizabeth Freilich, Sasikanth Manne, Victor Alcalde, Viktoriya Ekshyyan, Shelley L. Berger, Junwei Shi, Martha S. Jordan, E. John Wherry
Journal: Immunity (2023)
Identification of an IL-1 receptor mutation driving autoinflammation directs IL-1-targeted drug design
Authors: Yusha Wang, Jun Wang, Wenjie Zheng, Jiahui Zhang, Jinbo Wang, Taijie Jin, Panfeng Tao, Yibo Wang, Chenlu Liu, Jiqian Huang, Pui Y. Lee, Xiaomin Yu, Qing Zhou
Journal: Immunity (2023)
An astrocyte BMAL1-BAG3 axis protects against alpha-synuclein and tau pathology
Authors: Patrick W. Sheehan, Collin J. Nadarajah, Michael F. Kanan, Jessica N. Patterson, Brenna Novotny, Jennifer H. Lawrence, Melvin W. King, Logan Brase, Casey E. Inman, Carla M. Yuede, Jiyeon Lee, Tirth K. Patel, Oscar Harari, Bruno A. Benitez, Albert A. Davis, Erik S. Musiek
Journal: Neuron (2023)
Canonical BAF complex activity shapes the enhancer landscape that licenses CD8+ T cell effector and memory fates
Authors: Bryan McDonald, Brent Y. Chick, Nasiha S. Ahmed, Mannix Burns, Shixin Ma, Eduardo Casillas, Dan Chen, Thomas H. Mann, Carolyn O’Connor, Nasun Hah, Diana C. Hargreaves, Susan M. Kaech
Journal: Immunity (2023)
Abstract 2163: Long-term Follow-up (&gt;3 Years) of Patients Treated With Sirolimus-Eluting Stents for In-stent Restenosis. Results of a Randomized Study.
Authors: Fernando Alfonso, Maria J Perez-Vizcayno, Armando Bethencourt, Vicens Martí, Jose R Lopez-Minguez, Juan Angel, Andres Iñiguez, Cesar Moris, Angel Cequier, Cristina Fernandez
Journal: Circulation (2007)

Background: The value of drug-eluting stents in patients (P) with in-stent restenosis (ISR) has been established. However, the long-term results of this strategy in P with ISR remains unknown. Objective: We sought to determine the long-term clinical outcome of P treated with sirolimus-eluting stents (SES) for ISR. Methods: A systematic, pre-specified, long-term clinical follow-up (FU) was performed in all P included in the RIBS II (Restenosis Intra-stent: Balloon angioplasty [BA] vs elective SES implantation) randomized trial. In RIBS II 150 P with ISR after bare-metal stent implantation were included: 74 allocated to BA and 76 to SES. Late angiography was obtained in 96% of eligible P. A structured clinical questionnaire (cardiac/non cardiac death, myocardial infarction [MI], target vessel revascularization [TVR], thrombosis [TH], and medical therapy) was used during FU. Results: Angiographic restenosis (primary end-point) was more frequently found in the BA arm (39% vs 11%, p&lt;0.001). Clinical FU at 1-year was obtained in 150 P (100%). During this time period 6 P died (3 SES, 3 BA), 4 P suffered a MI (2 SES, 2 BA), 2 P experienced TH (1 P in each arm) and 30 required TVR (8 SES, 22 BA, p&lt;0.01). A complete clinical FU &gt;3 years was obtained in 145 P (97%) (mean 38±9 months, median 40 months [IQR 37–42]). Late events (after 1 year, non-exclusive) included: 3 deaths (1 SES, 2 BA), 3 MI (3 SES, 2 due to late TH) and 7 late TVR (5 SES, 2 BA). At 4 years, event-free survival was 76% in the SES arm and 65% in the BA arm (p=0.03). Survival free from TVR at 4 years was 80% in the SES arm and 67% in the BA arm (p=0.02). Conclusion: In P with ISR SES implantation improve the long-term clinical outcome as compared with BA treatment.
Europe's contribution to the evaluation of the use of systemic antimicrobials in the treatment of periodontitis
Authors: David Herrera, Arie Jan van Winkelhoff, Paula Matesanz, Katalina Lauwens, Wim Teughels
Journal: Periodontology 2000 (2023)

Abstract This narrative review celebrates Europe's contribution to the current knowledge on systemically administered antimicrobials in periodontal treatment. Periodontitis is the most frequent chronic noncommunicable human disease. It is caused by dysbiotic bacterial biofilms and is commonly treated with subgingival instrumentation. However, some sites/patients do not respond adequately, and its limitations and shortcomings have been recognized. This has led to the development of alternative or adjunctive therapies. One is the use of antimicrobials to target bacteria in subgingival biofilms in the periodontal pocket, which can be targeted directly through the pocket entrance with a locally delivered antibiotic or systemically by oral, intravenous, or intramuscular methods. Since the early 20th century, several studies on systemic antibiotics have been undertaken and published, especially between 1990 and 2010. Europe's latest contribution to this topic is the first European Federation of Periodontology, S3‐level Clinical Practice Guideline, which incorporates recommendations related to the use of adjuncts to treat stage I‐III periodontitis. Understanding the etiopathogenesis of periodontal diseases, specifically periodontitis, has influenced the use of systemic periodontal antibiotic therapy. Randomized clinical trials and systematic reviews with meta‐analyses have demonstrated the clinical advantages of adjunctive systemic antimicrobials. However, current recommendations are restrictive due to concerns about antibiotic misuse and the increase in microbial antibiotic resistance. European researchers have contributed to the use of systemic antimicrobials in the treatment of periodontitis through clinical trials and by providing rational guidelines. Nowadays, European researchers are exploring alternatives and directing clinical practice by providing evidence‐based guidelines to limit the use of systemic antimicrobials.
Immune profiling of murine cardiac leukocytes identifies triggering receptor expressed on myeloid cells 2 as a novel mediator of hypertensive heart failure
Authors: Charles Duncan Smart, Daniel J Fehrenbach, Jean W Wassenaar, Vineet Agrawal, Niki L Fortune, Debra D Dixon, Matthew A Cottam, Alyssa H Hasty, Anna R Hemnes, Amanda C Doran, Deepak K Gupta, Meena S Madhur
Journal: Cardiovascular Research (2023)

Abstract Aims Heart failure with preserved ejection fraction (HFpEF) is characterized by diastolic dysfunction, microvascular dysfunction, and myocardial fibrosis with recent evidence implicating the immune system in orchestrating cardiac remodelling. Methods and results Here, we show the mouse model of deoxycorticosterone acetate (DOCA)-salt hypertension induces key elements of HFpEF, including diastolic dysfunction, exercise intolerance, and pulmonary congestion in the setting of preserved ejection fraction. A modified single-cell sequencing approach, cellular indexing of transcriptomes and epitopes by sequencing, of cardiac immune cells reveals an altered abundance and transcriptional signature in multiple cell types, most notably cardiac macrophages. The DOCA-salt model results in differential expression of several known and novel genes in cardiac macrophages, including up-regulation of Trem2, which has been recently implicated in obesity and atherosclerosis. The role of Trem2 in hypertensive heart failure, however, is unknown. We found that mice with genetic deletion of Trem2 exhibit increased cardiac hypertrophy, diastolic dysfunction, renal injury, and decreased cardiac capillary density after DOCA-salt treatment compared to wild-type controls. Moreover, Trem2-deficient macrophages have impaired expression of pro-angiogenic gene programmes and increased expression of pro-inflammatory cytokines. Furthermore, we found that plasma levels of soluble TREM2 are elevated in DOCA-salt treated mice and humans with heart failure. Conclusions Together, our data provide an atlas of immunological alterations that can lead to improved diagnostic and therapeutic strategies for HFpEF. We provide our dataset in an easy to explore and freely accessible web application making it a useful resource for the community. Finally, our results suggest a novel cardioprotective role for Trem2 in hypertensive heart failure.
BIOL-17. DISSECTING THE EXPRESSION AND FUNCTION OF ANGIOPOIETIN-1 IN PEDIATRIC BRAIN TUMORS
Authors: Jaldeep Langhnoja, Xin Wei, Phonepasong Arounleut, Ipsita Kundu, Timothy Phoenix
Journal: Neuro-Oncology (2023)

Abstract BACKGROUND Angiopoietin-1 (Angpt1) is a secreted protein that promotes angiogenesis and vascular stability in development and certain disease states through activation of the Tie2 receptor. However, little is known about its expression or function within pediatric brain tumors. METHODS We utilized available datasets from patient samples and created murine models of pediatric high-grade glioma and ependymoma by in utero electroporation. Using a combination of transcriptomics and Angpt1-GFP reporter tumor models we evaluated Angpt1 expression across different types of pediatric brain tumors. We also applied inducible Angpt1 floxed mice to generate tumor-specific knock-out models. RESULTS Angpt1 is upregulated in glial brain tumors, including high-grade gliomas and ependymomas. We find Angpt1 is expressed by specific cell populations within gliomas and ependymomas, along with non-tumor reactive astrocytes and perivascular mural cells. Leveraging our in vivo brain tumor platform we have created tumor specific Angpt1 knock-out models by including a plasmid expressing Cre-recombinase. Ongoing studies aim to delineate the function of Angpt1 in tumor pathogenesis, including tumor angiogenesis and blood-brain barrier function. CONCLUSION Current work finds that Angpt1 is upregulated in glial brain tumors and nominates it as a potential modulator of brain tumor vascular biology, including tumor angiogenesis and permeability.
LPS adsorption and inflammation alleviation by polymyxin B-modified liposomes for atherosclerosis treatment
Authors: Huiwen Liu, Honglan Wang, Qiyu Li, Yiwei Wang, Ying He, Xuejing Li, Chunyan Sun, Onder Ergonul, Füsun Can, Zhiqing Pang, Bo Zhang, Yu Hu
Journal: Acta Pharmaceutica Sinica B (2023)

Chronic inflammation is critical in the onset and progression of atherosclerosis (AS). The lipopolysaccharide (LPS) level in the circulation system is elevated in AS patients and animal models, which is correlated with the severity of AS. Inspired by the underlying mechanism that LPS could drive the polarization of macrophages toward the M1 phenotype, aggravate inflammation, and ultimately contribute to the exacerbation of AS, LPS in the circulation system was supposed to be the therapeutic target for AS treatment. In the present study, polymyxin (PMB) covalently conjugated to PEGylated liposomes (PLPs) were formulated to adsorb LPS through specific interactions between PMB and LPS. In vitro, the experiments demonstrated that PLPs could adsorb LPS, reduce the polarization of macrophages to M1 phenotype and inhibit the formation of foam cells. In vivo, the study revealed that PLPs treatment reduced the serum levels of LPS and pro-inflammatory cytokines, decreased the proportion of M1-type macrophages in AS plaque, stabilized AS plaque, and downsized the plaque burdens in arteries, which eventually attenuated the progression of AS. Our study highlighted LPS in the circulation system as the therapeutic target for AS and provided an alternative strategy for AS treatment.
Transformative Materials to Create 3D Functional Human Tissue Models In Vitro in a Reproducible Manner
Authors: Jose L. Gerardo‐Nava, Jitske Jansen, Daniel Günther, Laura Klasen, Anja Lena Thiebes, Bastian Niessing, Cédric Bergerbit, Anna A. Meyer, John Linkhorst, Mareike Barth, Payam Akhyari, Julia Stingl, Saskia Nagel, Thomas Stiehl, Angelika Lampert, Rudolf Leube, Matthias Wessling, Francesca Santoro, Sven Ingebrandt, Stefan Jockenhoevel, Andreas Herrmann, Horst Fischer, Wolfgang Wagner, Robert H. Schmitt, Fabian Kiessling, Rafael Kramann, Laura De Laporte
Journal: Advanced Healthcare Materials (2023)

Abstract Recreating human tissues and organs in the petri dish to establish models as tools in biomedical sciences has gained momentum. These models can provide insight into mechanisms of human physiology, disease onset, and progression, and improve drug target validation, as well as the development of new medical therapeutics. Transformative materials play an important role in this evolution, as they can be programmed to direct cell behavior and fate by controlling the activity of bioactive molecules and material properties. Using nature as an inspiration, scientists are creating materials that incorporate specific biological processes observed during human organogenesis and tissue regeneration. This article presents the reader with state‐of‐the‐art developments in the field of in vitro tissue engineering and the challenges related to the design, production, and translation of these transformative materials. Advances regarding (stem) cell sources, expansion, and differentiation, and how novel responsive materials, automated and large‐scale fabrication processes, culture conditions, in situ monitoring systems, and computer simulations are required to create functional human tissue models that are relevant and efficient for drug discovery, are described. This paper illustrates how these different technologies need to converge to generate in vitro life‐like human tissue models that provide a platform to answer health‐based scientific questions.
Global incidence in hospital-associated infections resistant to antibiotics: An analysis of point prevalence surveys from 99 countries
Authors: Ruchita Balasubramanian, Thomas P. Van Boeckel, Yehuda Carmeli, Sara Cosgrove, Ramanan Laxminarayan
Journal: PLoS Medicine (2023)

Background Hospital-associated infections (HAIs) are an important cause of morbidity and mortality around the world. Many HAIs are caused by drug-resistant bacterial pathogens, but there are major gaps in our understanding of the number of hospital-associated drug-resistant infections (HARIs) worldwide. As such, we estimated trends in prevalence of HARIs caused by high priority pathogens ( Escherichia coli , Acinetobacter spp., Klebsiella spp., Staphylococcus aureus , Enterobacter spp., and Pseudomonas spp.) in 195 countries. Methods and findings Resistance prevalence estimates were extracted from 474-point prevalence surveys (PPS) from 99 countries published between 2010 and 2020 coupled with country-level estimates of hospitalization rates and length of stay. Prevalence estimates were transformed in yearly incidence of HARIs per year by country and income group. We estimate the global number of HARIs per year to be 136 million (95% credible interval (CI) 26 to 246 million) per year, with the highest burden in China (52 million, 95% CI 10 to 95 million), Pakistan (10 million, 95% CI 2 to 18 million), and India (9 million, 95% CI 3 to 15 million). Among income groups, middle-income countries bore the highest burden of HARIs per year (119 million, 95% CI 23 to 215 million). Our analysis was constrained by the limited number of PPS for HARIs, lack of community-associated data on antibiotic-resistant infections, and our population level analysis. Conclusions In this study, we observe, in the absence of systematic surveillance systems for HARIs, a baseline overview of their rates. Our yearly estimates highlight the global threat of HARIs and may help define strategies to tackle resistance in hospital settings.
Combination of AAV-delivered tumor suppressor PTEN with anti-PD-1 loaded depot gel for enhanced antitumor immunity
Authors: Yongshun Zhang, Lan Yang, Yangsen Ou, Rui Hu, Guangsheng Du, Shuang Luo, Fuhua Wu, Hairui Wang, Zhiqiang Xie, Yu Zhang, Chunting He, Cheng Ma, Tao Gong, Ling Zhang, Zhirong Zhang, Xun Sun
Journal: Acta Pharmaceutica Sinica B (2023)

Recent clinical studies have shown that mutation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) gene in cancer cells may be associated with immunosuppressive tumor microenvironment (TME) and poor response to immune checkpoint blockade (ICB) therapy. Therefore, efficiently restoring PTEN gene expression in cancer cells is critical to improving the responding rate to ICB therapy. Here, we screened an adeno-associated virus (AAV) capsid for efficient PTEN gene delivery into B16F10 tumor cells. We demonstrated that intratumorally injected AAV6-PTEN successfully restored the tumor cell PTEN gene expression and effectively inhibited tumor progression by inducing tumor cell immunogenic cell death (ICD) and increasing immune cell infiltration. Moreover, we developed an anti-PD-1 loaded phospholipid-based phase separation gel (PPSG), which formed an
Bias in AI-based models for medical applications: challenges and mitigation strategies
Authors: Mirja Mittermaier, Marium M. Raza, Joseph C. Kvedar
Journal: npj Digital Medicine (2023)

Artificial intelligence systems are increasingly being applied to healthcare. In surgery, AI applications hold promise as tools to predict surgical outcomes, assess technical skills, or guide surgeons intraoperatively via computer vision. On the other hand, AI systems can also suffer from bias, compounding existing inequities in socioeconomic status, race, ethnicity, religion, gender, disability, or sexual orientation. Bias particularly impacts disadvantaged populations, which can be subject to algorithmic predictions that are less accurate or underestimate the need for care. Thus, strategies for detecting and mitigating bias are pivotal for creating AI technology that is generalizable and fair. Here, we discuss a recent study that developed a new strategy to mitigate bias in surgical AI systems.
Recurrent infection transiently expands human tissue T cells while maintaining long-term homeostasis
Authors: Veronica Davé, Laura E. Richert-Spuhler, Tanvi Arkatkar, Lakshmi Warrier, Thepthara Pholsena, Christine Johnston, Joshua T. Schiffer, Martin Prlic, Jennifer M. Lund
Journal: The Journal of Experimental Medicine (2023)

Chronic viral infections are known to lead to T cell exhaustion or dysfunction. However, it remains unclear if antigen exposure episodes from periodic viral reactivation, such as herpes simplex virus type-2 (HSV-2) recrudescence, are sufficient to induce T cell dysfunction, particularly in the context of a tissue-specific localized, rather than a systemic, infection. We designed and implemented a stringent clinical surveillance protocol to longitudinally track both viral shedding and in situ tissue immune responses in a cohort of HSV+ volunteers that agreed to avoid using anti-viral therapy for the course of this study. Comparing lesion to control skin biopsies, we found that tissue T cells expanded immediately after reactivation, and then returned numerically and phenotypically to steady state. T cell responses appeared to be driven at least in part by migration of circulating T cells to the infected tissue. Our data indicate that tissue T cells are stably maintained in response to HSV reactivation, resembling a series of acute recall responses.
FDG PET (and MRI) for Monitoring Immunotherapy in Alzheimer Disease
Authors: Poul F. Høilund-Carlsen, Mona-Elisabeth Revheim, Abass Alavi, Jorge R. Barrio
Journal: Clinical Nuclear Medicine (2023)

Abstract Passive immunotherapy for Alzheimer disease has been tried for over 10 years without success. However, in 2021 and most recently in January 2023, the US Food and Drug Administration granted accelerated approval of 2 antibodies for this purpose, aducanumab and lecanemab. In both cases, the approval was based on a presumed therapy-related removal of amyloid deposits from the brain and, in the case of lecanemab, also some delay in cognitive decline. We question the validity of the evidence for the removal of amyloid in particular as assessed by amyloid PET imaging, believing that what is observed is more likely a large nonspecific amyloid PET signal in the white matter that diminishes during immunotherapy—in line with dose-dependent increases in amyloid-related imaging abnormalities and increased loss of cerebral volume in treated compared with placebo patients. To investigate this further, we recommend repeat FDG PET and MRI in all future immunotherapy trials.
Lymphoscintigraphy of the Lower Extremities
Authors: Lubomir Mrhac, Martin Havel, Michal Kolacek, Otakar Kraft, Kamil Bukovansky
Journal: Clinical Nuclear Medicine (2023)

We describe a 57-year-old man with prostate cancer. A radical prostatectomy with a pelvic lymphadenectomy was performed. After 2 years, a mild swelling of the lower extremities appeared, and the patient was referred for lower-limb lymphoscintigraphy. A lymphoscintigraphy of the superficial lymphatic system in the limbs showed prominent, dermal backflow in the area of the right hypogastrium. Lymphoscintigraphy of the deep lymphatic system showed reflux in the left hypogastrium. This discrepancy between the findings in the superficial and deep lower-limb lymphatic systems was explained by asymmetric sampling of the lymph nodes during the lymphadenectomy.
Comparison of Translocator Protein Expression Between Tumefactive Multiple Sclerosis and Glioblastoma
Authors: Per Jensen, Morten Blinkenberg, Lars Hageman Pinborg
Journal: Clinical Nuclear Medicine (2023)

This figure presents a comparison of molecular imaging of the translocator protein (TSPO) and contrast-enhanced MRI in 2 patients with tumefactive multiple sclerosis and glioblastoma, respectively. In the case of the tumefactive multiple sclerosis patient, TSPO uptake is primarily located centrally, while in the glioblastoma patient, TSPO uptake is predominantly situated peripherally to the central necrotic area. These findings suggest that TSPO imaging could be a noninvasive imaging technique for distinguishing between these 2 diagnoses.
Enzyme‐Triggered Intestine‐Specific Targeting Adhesive Platform for Universal Oral Drug Delivery
Authors: Ying Li, Jung Seung Lee, Ameya R. Kirtane, Mengyuan Li, Charles William Coffey, Kaitlyn Hess, Aaron Lopes, Joy Collins, Siddartha Tamang, Keiko Ishida, Alison Hayward, Jacob Wainer, Adam J. Wentworth, Giovanni Traverso
Journal: Advanced Healthcare Materials (2023)

Patient adherence to chronic therapies can be suboptimal, leading to poor therapeutic outcomes. Dosage forms that enable reduction in dosing frequency stand to improve patient adherence. Variation in gastrointestinal transit time, inter-individual differences in gastrointestinal physiology and differences in physicochemical properties of drugs represent challenges to the development of such systems. To this end, a small intestine-targeted drug delivery system is developed, where prolonged gastrointestinal retention and sustained release are achieved through tissue adhesion of drug pills mediated by an essential intestinal enzyme catalase. Here proof-of-concept pharmacokinetics is demonstrated in the swine model for two drugs, hydrophilic amoxicillin and hydrophobic levodopa. It is anticipated that this system can be applicable for many drugs with a diverse of physicochemical characteristics.